Fulminant Type 1 Diabetes Mellitus Associated with Coxsackie Virus Type A2 Infection: A Case Report and Literature Review.

A 65-year-old Japanese man presented to our hospital in June 2013 with a 6-day history of fever and fatigue, a 24-h history of thirst, and polyuria. His temperature was 37.8°C and he was alert. However, laboratory tests revealed severe hyperglycemia, undetectable C-peptide levels, and diabetic ketoacidosis. Serum antibody testing confirmed a Coxsackie virus A2 infection. A variety of viral infections are reported to be involved in the development of fulminant type 1 diabetes mellitus (FT1D). Our patient is the first reported case of FT1D associated with Coxsackie virus A2 infection and supports the etiological role of common viral infections in FT1D.

[A case of mediastinal growing teratoma syndrome with acute megakaryoblastic leukemia].

We report a case of a 38-year-old man who was diagnosed with a mediastinal germ cell tumor. After induction chemotherapy, the tumor marker levels normalized, but the tumor itself continued to grow. Surgical resection was performed successfully, but the patient developed acute megakaryoblastic leukemia 6 months later, and induction and consolidation therapies failed to achieve remission. Leukemia cells invaded the central nervous system following hematopoietic stem cell transplantation, and the patient died 5 months after being diagnosed with leukemia. This very rare case of a mediastinal germ cell tumor met the criteria for "growing teratoma syndrome", against a background of acute megakaryoblastic leukemia.

[Two cases of IgG4-related disease with pleural effusion].

We describe 2 cases of IgG4-related disease with pleural effusion in elderly men. Both patients had elevated serum IgG4 levels, and the characteristics of their pleural effusion were similar. Patient 1 had pericardial effusion and retroperitoneal fibrosis, and a biopsy specimen from the pericardium showed infiltration of abundant IgG4-positive plasma cells with fibrosis. Because his pleurisy, pericarditis and retroperitoneal fibrosis responded to steroid therapy, we diagnosed pleurisy associated with IgG4-related disease. Patient 2 had been treated with steroids because of IgG4-related sialadenitis and interstitial pneumonitis, but pleural effusion developed. Although histopathological examination of the pleura showed infiltration of abundant IgG4-positive plasma cells with fibrosis, Mycobacterium tuberculosis was cultured from the pleural effusion, and histologic examination also showed epithelioid granuloma. Chemotherapy for tuberculosis was effective for the pleurisy, and we diagnosed tuberculous pleurisy as a complication of IgG4-related disease. In cases of IgG4-related disease associated with pleural effusion, the clinical course should be considered together with the serum IgG4 levels and pleural histology.

Chikungunya virus isolated from a returnee to Japan from Sri Lanka: isolation of two sub-strains with different characteristics.

A large-scale epidemic of chikungunya (CHIK) fever occurred in several Indian Ocean islands in 2004 and spread to India and Sri Lanka. In December 2006, a returnee to Japan from Sri Lanka developed an acute febrile illness. The patient was confirmed to have CHIK fever after reverse transcription-polymerase chain reaction, and specific IgM and IgG detection. CHIK virus was isolated from the serum specimen collected at the acute stage. The isolated virus developed two different sizes of plaques. Two sub-strains with different genetic and biological characteristics were obtained by plaque purification from one isolate. The entire genome was sequenced and phylogenetic analysis of the E1 genome showed that the sub-strains were of the Central/East African genotype, and were closely related to recent isolates in India. This is the first report of CHIK virus genome sequences isolated from a patient infected in Sri Lanka.

Laparoscopic peritoneal biopsy can be crucial for diagnosis of tuberculous peritonitis.

A 28-year-old woman was admitted to a nearby hospital because of low-grade fever and lower abdominal pain, where ascites and slightly elevated serum CA125 level were found. Both acid-fast stain (AFS) and polymerase chain reaction (PCR) failed to detect Mycobacterium tuberculosis in her ascitic fluid, sputum, and gastric juice. She was referred to our division under suspicion of tuberculous peritonitis or ovarian carcinoma. Finally, diagnostic laparoscopy was carried out, showing yellowish-white small nodules disseminated on her whole peritoneum with thin fibrous adhesions. Peritoneal biopsy of these nodules showed epithelioid cell granulomas without caseous necrosis. AFS and PCR again failed to show any evidence of Mycobacterium tuberculosis in these biopsied samples. Based on the laparoscopic findings, however, we thought that she suffered from tuberculous peritonitis. Antituberculous therapy was started and she improved soon. Later, Mycobacterium tuberculosis was demonstrated in the 4-week culture of a peritoneal biopsy specimen. We conclude that laparoscopy may be the only way to detect Mycobacterium tuberculosis in tuberculous peritonitis whenever doubtful but no direct evidence is obtained.

Cutting edge: role of STAT1, STAT3, and STAT5 in IFN-alpha beta responses in T lymphocytes.

Engagement of the IFN-alphabeta receptor initiates multiple signaling cascades, including activation of the STAT. In this study, we demonstrate that IFN-alphabeta, although antiproliferative in wild-type CD4(+) or CD8(+) T cells, act as strong mitogens on their STAT1(-/-) counterparts. Furthermore, IFN-alphabeta exert little effect on apoptosis in wild-type cells, but are potent survival factors in the absence of STAT1. The antiapoptotic response in the absence of STAT1 is predominantly mediated by STAT3, and to a lesser extent by STAT5A/B. In contrast, the mitogenic IFN-alphabeta response gained through the absence of STAT1 is only marginally affected when STAT5A/B expression is also abrogated, but is completely dependent on STAT3 activation. These findings provide the first evidence for a function of STAT3 and STAT5A/B in the IFN-alphabeta response, and support a model in which the IFN-alphabeta receptor initiates both pro- and antiapoptotic responses through STAT1, and STAT3 and STAT5A/B, respectively.

[Pneumocystis carinii pneumonia complicating brain tumor].

Brain tumors are frequently treated with steroids due to the presence of peritumoral edema. However, in Japan it is not widely recognized that primary brain tumor patients who are receiving steroid therapy become susceptible to Pneumocystis carinii pneumonia (PCP). We reviewed the clinical features and risk factors for PCP in brain tumor patients treated at our institution between 1994 and 2002. The treated cases consisted of 6 men and 6 women ranging in age from 47 to 78 yr (mean age 65.3). Underlying diseases included malignant glioma in 9 patients, malignant lymphoma in 2 patients and meningioma in one patient. All were diagnosed by respiratory disease specialists using bronchial washings and bronchoalveolar lavage or chest X ray/CT image. Radiation therapies were administered with 20 to 60 Gy (mean 52.9 Gy) except in one patient. Chemotherapy was performed with ranimustine in 4 malignant glioma patients and with methotrexate in 2 malignant lymphoma patients. Prednisone, begun perioperatively, was reduced gradually from a mean initial dosage of 38.3 mg/day orally. The duration of steroid treatment at the onset of PCP in these patients ranged from 41 to 79 days (mean 61.4 days). Six patients (50%) died of PCP despite appropriate antibiotic therapy and 2 patients needed intensive therapy with a respirator. For early diagnosis of PCP, periodic serological (e.g.; the level of lactate dehydrogenase and beta-D-glucan) and radiological examination (e.g.; chest X ray and CT image) is indicated in patients with brain tumors, and prophylaxis against PCP might be needed for patients with intracranial neoplasms and who are also receiving high-dose and long-term steroid treatment.

Impaired development of CD4+ CD25+ regulatory T cells in the absence of STAT1: increased susceptibility to autoimmune disease.

Type I and II interferons (IFNs) exert opposing effects on the progression of multiple sclerosis, even though both IFNs use the signal transducer and activator of transcription 1 (STAT1) as a signaling mediator. Here we report that STAT1-deficient mice expressing a transgenic T cell receptor against myelin basic protein spontaneously develop experimental autoimmune encephalomyelitis with dramatically increased frequency. The heightened susceptibility to this autoimmune disease appears to be triggered by a reduced number as well as a functional impairment of the CD4+ CD25+ regulatory T cells in STAT1-deficient animals. Adoptive transfer of wild-type regulatory T cells into STAT1-deficient hosts is sufficient to prevent the development of autoimmune disease. These results demonstrate an essential role of STAT1 in the maintenance of immunological self-tolerance.

Rhabdomyolysis after simvastatin therapy in an HIV-infected patient with chronic renal failure.

We encountered a 49-year-old HIV-infected man with chronic renal insufficiency who developed rhabdomyolysis after treatment with simvastatin. He recovered after initiating hemodialysis and discontinuing oral medications. Rhabdomyolysis most likely resulted from an excessive blood concentration of simvastatin caused by concomitant use of fluconazole in the presence of renal insufficiency.